Role of microRNAs in obesity and obesity-related diseases (original) (raw)
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Biomedicines, 2021
Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity ac...
Significant role of some miRNAs as biomarkers for the degree of obesity
Journal of Genetic Engineering and Biotechnology
Background Obesity is one of the most serious problems over the world. MicroRNAs have developed as main mediators of metabolic processes, playing significant roles in physiological processes. Thus, the present study aimed to evaluate the expressions of (miR-15a, miR-Let7, miR-344, and miR-365) and its relationship with the different classes in obese patients. Methods A total of 125 individuals were enrolled in the study and classified into four groups: healthy non-obese controls (n = 50), obese class I (n = 24), obese class II (n = 17), and obese class III (n = 34) concerning body mass index (BMI < 30 kg/m2, BMI 30–34.9 kg/m2, BMI 35–39.9 kg/m2 and BMI ≥ 40 kg/m2, respectively). BMI and the biochemical measurements (fasting glucose, total cholesterol, triglycerides, HDL and LDL, urea, creatinine, AST, and ALT) were determined. The expressions of (miR-15a, miR-Let7, miR-344, and miR-365) were detected through quantitative real-time PCR (RT-qPCR). Results There was a significant di...
Targeting the Circulating MicroRNA Signature of Obesity
Clinical Chemistry, 2013
BACKGROUND: Genomic studies have yielded important insights into the pathogenesis of obesity. Circulating microRNAs (miRNAs) are valuable biomarkers of systemic diseases and potential therapeutic targets. We sought to define the circulating pattern of miRNAs in obesity and examine changes after weight loss.
An Update on Microrna’s and Metabolic Regulation with Future Therapeutic PotentialsRegarding Diagnosis and Treatment of Obesity, Metabolic Syndrome and Other Related Disorders. J Health Med Informat 6: 184. doi: 10.4172/2157-7420.1000184, 2015
Micro RNAs is a family of highly conserved, single stranded 19- 23 nucleotide long noncoding endogenous RNAs which negatively regulate gene expression, either by inhibiting translation or by degrading largest mRNAs [1]. Over 2000 unique miRNAs have been identified in humans [2] The miRNAs are initially transcribed as long RNA precursors termed primary miRNAs (pri-miRNAs) that require the RNAse III enzyme Drosha in the nucleus to trim them into premiRNAs The premiRNAs are characterized by a stemloop or hairpin structure of 70-100 nucleotides and are exported to the cytoplasm by the nuclear export factor exportin 5. The pre-miRNAs are subsequently cropped to become mature miRNA by another RNAse enzyme Dicer in the cytoplasm [3]. Although our understanding of the specific roles of miRNAs in cellular function is only beginning, recent studies revealed that miRNAs play a pivotal role in the most critical biological events such as development, proliferation, differentiation, apoptosis, transductionand carcinogenesis [4].The mature miRNA’s are conserved about 2 nucleotides noncoding RNAs that anneal to inexactly complementary sequences in the 3’untranslated regions(3’UTR) of target mRNA of protein coding genes, resulting in silencing of the target gene.While the mechanism of action of miRNAs is yet to be fully understood , the widely known mode of gene regulation by miRNAs occurs at the post transcriptional level by either specific inhibition of translation or induction of mRNACleavage [5,6], resulting in a reduction in protein levels of their targets (Figure1) [7]. Alternatively, if the expression of miRNA’s is inhibited, then increased protein expression may be seen in animal species. miRNAs are also capable of modifying chromatin (Figure1) [6]. dsRNA miRNA complex which is composed of the mature miR and its passenger strand (miR”) is unwound by helicase activities of the Argonaute (Ago) multiprotein complex, globally known as the RNA-induced silencing complex (RISC) [8-10]. Determination of the active (guide) strandis based upon simple energetics between strands at the 5’ ends of the dsRNA complex [11]. The preferred guide strand is subsequently incorporated-Furthermore we detailed role of miR in adipose tissue ,obesity,IR,childhood obesity&in adulthood besides role of specific miR'S
PloS one, 2012
Obesity is a major health concern worldwide which is associated with increased risk of chronic diseases such as metabolic syndrome, cardiovascular disease and cancer. The elucidation of the molecular mechanisms involved in adipogenesis and obesogenesis is of essential importance as it could lead to the identification of novel biomarkers and therapeutic targets for the development of anti-obesity drugs. MicroRNAs (miRNAs) have been shown to play regulatory roles in several biological processes. They have become a growing research field and consist of promising pharmaceutical targets in various fields such as cancer, metabolism, etc. The present study investigated the possible implication of miRNAs in adipose tissue during the development of obesity using as a model the C57BLJ6 mice fed a high-fat diet. C57BLJ6 wild type male mice were fed either a standard (SD) or a high-fat diet (HFD) for 5 months. Total RNA was prepared from white adipose tissue and was used for microRNA profiling and qPCR. Twenty-two of the most differentially expressed miRNAs, as identified by the microRNA profiling were validated using qPCR. The results of the present study confirmed previous results. The upregulation of mmu-miR-222 and the down-regulation of mmu-miR-200b, mmu-miR-200c, mmu-miR-204, mmu-miR-30a*, mmu-miR-193, mmu-miR-378 and mmu-miR-30e* after HFD feeding has also been previously reported. On the other hand, we show for the first time the up-regulation of mmu-miR-342-3p, mmu-miR-142-3p, mmu-miR-142-5p, mmu-miR-21, mmu-miR-146a, mmu-miR-146b, mmu-miR-379 and the down-regulation of mmu-miR-122, mmu-miR-133b, mmu-miR-1, mmu-miR-30a*, mmu-miR-192 and mmu-miR-203 during the development of obesity. However, future studies are warranted in order to understand the exact role that miRNAs play in adipogenesis and obesity.
MicroRNAs in adipogenesis and as therapeutic targets for obesity
Expert Opinion on Therapeutic Targets, 2011
Introduction-Obesity and obesity-related disease have reached pandemic proportions and are prevalent even in developing countries. Adipose tissue is increasingly being recognized as a key regulator of whole-body energy homeostasis and consequently as a prime therapeutic target for metabolic syndrome. This review discusses the roles of miRNAs, small endogenously expressed RNAs that regulate gene expression at a post-transcriptional level, in the development and function of adipose tissue and other relevant metabolic tissues impacted by obesity. Several highthroughput studies have identified hundreds of miRNAs that are differentially expressed during the development of metabolic tissues or as an indication of pathophysiology. Further investigation has functionalized the regulatory capacity of individual miRNAs and revealed putative targets for these miRNAs. Therefore, as with several other pathologies, miRNAs are emerging as feasible therapeutic targets for metabolic syndrome.
The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity
Pediatric Obesity, 2015
Background: Childhood obesity is an increasing health challenge related to increased risk of chronic diseases. microRNAs (miRNAs) are noncoding short RNA molecules regulating multiple biological processes linked to obesity. Objectives: We aimed at evaluating the association between circulating miRNA levels and lipid metabolism in obese and non-obese children and adolescents. Methods: By constituting study group, 45 obese children and adolescents were recruited. To perform comparisons with study group, 41 lean controls were matched for age and sex. Using real-time quantitative PCR analysis, circulating miRNAs were evaluated in both groups. Results: Circulating miR-335 (P < 0.001), miR-143 (P = 0.001) and miR-758 (P = 0.006) in obese children were significantly lower than those of controls. However, circulating miR-27 (P = 0.032), miR-378 (P < 0.001) and miR-370 (P = 0.045) in obese children were significantly higher, compared with those of controls. In addition, circulating miR-33 in obese children was higher than those of controls, but no significant difference was present (P = 0.687). Conclusion: Our findings showed that a significant association is present between circulating miR-370, miR-33, miR-378, miR-27, miR-335, miR-143 and miR-758 values, and childhood obesity. Low levels of miR-335, miR-143 and miR-758, and high levels of miR-27, miR-378, miR-33 and miR-370 may have been responsible for elevated triglycerides and low-density lipoprotein (LDL-C) levels, and low level of high-density lipoprotein (HDL-C) in obese subjects. Therefore, miRNAs may be a good novel biomarker for childhood obesity.
Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies
Journal of Endocrinological Investigation, 2020
Background Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weightloss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. Aim The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. Results A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. Conclusions Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity.
Frontiers in Endocrinology
BackgroundObesity-associated dysglycemia is associated with metabolic disorders. MicroRNAs (miRNAs) are known regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with clinical features in obese Qatari individuals.MethodsWe analyzed a dataset of 39 age-matched patients that includes 18 subjects with obesity only (OBO) and 21 subjects with obesity and metabolic syndrome (OBM). We measured 754 well-characterized human microRNAs (miRNAs) and identified differentially expressed miRNAs along with their significant associations with clinical markers in these patients.ResultsA total of 64 miRNAs were differentially expressed between metabolically healthy obese (OBO) versus metabolically unhealthy obese (OBM) patients. Thirteen out of 64 miRNAs significantly correlated with at least one clinical trait of the metabolic syndrome. Six out of the thirteen demonstrated significant association with HbA1c levels; miR-331-3p, miR-452-3p, and miR-485-5p were...
MicroRNAs and metabolic disorders - where are we heading?
Archives of medical science : AMS, 2017
MicroRNAs (miRNAs, miRs) are short, non-coding molecules engaged in normal functioning of eukaryotic cells, as negative regulators of gene expression. Since the first discovery of miRNA in the early 1990s, hundreds of different miRNAs and their targets have been identified. A growing number of studies have aimed to search for microRNAs which have a key role in the regulation of insulin signaling and metabolic homeostasis. Recent evidence indicates that dysregulation of miRNA expression is involved in the development of various diseases, including type 2 diabetes mellitus (T2DM), obesity and cardiovascular diseases. This review summarizes the biogenesis of miRNAs and their role in pancreatic β cell biology, insulin signaling and metabolism. We also discuss recent findings of miRNAs associated with metabolic disorders and vascular diabetic complications, their diagnosis and therapeutic value. The PubMed database and published reference lists were searched for articles published betwee...